ephedra.com - ephedra petition for rehearing

IN THE UNITED STATES COURT OF APPEALS
FOR THE TENTH CIRCUIT
____________________
NUTRACEUTICAL CORPORATION, et al.,
Plaintiffs-Appellees,
v.
ANDREW VON ESCHENBACH, Acting Commissioner,
U.S. Food and Drug Administration, et al.,
Defendants-Appellants.
____________________
ON APPEAL FROM THE UNITED STATES DISTRICT COURT
FOR THE DISTRICT OF UTAH
The Honorable Tena Campbell
____________________
APPELLEES' PETITION FOR REHEARING OR REHEARING EN BANC
________________

JONATHAN W. EMORD* ANDREA G. FERRENZ Emord & Associates, P.C. 1800 Alexander Bell Dr., S.200 Reston, VA 20191 (202) 466-6937	RICHARD A. EPSTEIN 111 East 60th St. Chicago, IL 60637 (773) 702-9563
MARCY G. GLENN Holland & Hart LLP 555 17th Street, S. 3200 Denver, CO 80202 303-295-8320

TABLE OF AUTHORITIES..................................................................................iii
STATEMENT OF COUNSEL UNDER F.R.A.P. 35(b) ...................................... 1
BACKGROUND AND INTRODUCTION.......................................................... 2
THE PANEL DECISION ..................................................................................... 6
ARGUMENT ...................................................................................................... 10
A. The Panel's "Unreasonable Risk" Definition Violates the Supreme Court's
Statutory Construction Precedent........................................................................... 10
B. The Panel's Decision Involves Questions of Exceptional Importance .................. 13
CONCLUSION................................................................................................... 15

Case Law
American Textile Mfr. Inst. v. Donovan, 452 U.S. 490 (1981) .............................. 12
Chevron USA Inc. v. Natural Resources Defense Council Inc.,
467 U.S. 837 (1984) ......................................................................................passim
Chickasaw Nation v. United States, 534 U.S. 84 (2001) ......................................... 7
Citizens to Preserve Overton Park, Inc. v. Volpe, 401 U.S. 402 (1971)............... 1,15
Demarest v. Manspeaker, 498 U.S. 184 (1991) ................................................. 1,12
Estate of Cowart v. Nicklos Drilling Co., 505 U.S. 469 (1992)............................ 1,12
FDA v. Brown & Williamson Tobacco, 529 U.S. 120 (2000).............................. 1,12
Fleming v. Florida Citrus Exchange, 358 U.S. 153 (1958)......................................... 8
Garcia v. United States, 469 U.S. 70, 76 (1984) .................................................... 11
Gonzales v. Oregon, 126 S.Ct. 904 (2006).......................................................... 1,12
Lamie v. United States Trustee, 540 U.S. 526 (2004)................................................ 7
Merck KGaA v. Integra Life Sciences I., Ltd., 125 S.Ct. 2372 (2005)...............passim
Nutraceutical v. Crawford, 364 F.Supp.2d 1310 (D.Ut. 2005) .............................. 2,6
Pharmanex v. Shalala, 221 F.3d 1151 (10th Cir. 2000) .......................................... 11
Russello v. United States, 464 U.S. 16 (1983). .....................................................1,12
Scheidler v. National Organization for Women, Inc., 126 S.Ct. 1264 (2006) ............. 7
United States v. Anderson Seafoods, 622 F.2d 157 (5th Cir. 1980) ................... 11,14
United States v. Boston Farm Center, 590 F.2d 149 (5th Cir. 1974)........................ 11
United States v. Lexington Mill & Elevator Co., 232 U.S. 399 (1914) .................. 8,14
Whitaker v. American Trucking Ass'n, 531 U.S. 457 (2001)................................. 1,12

Statutes
The Dietary Supplement Health and Education Act (DSHEA),
Pub.L.No. 103-417, 108 Stat. 4325 (1994) ........................................................ 2,13
The Federal Food, Drug, and Cosmetic Act (FDCA), 21 USC 321 et seq. ........passim
21 USC 321(p)........................................................................................................10
21 USC 321(ff) .................................................................................................passim
21 USC 342(f)(1)(A)(i) .....................................................................................passim
21 USC 342 ..................................................................................................... 7,9,10
21 USC 350b ..........................................................................................................10
21 USC 355 ........................................................................................................... 10
21 USC 355(b)(1)(A)................................................................................................ 8
21 USC 355(i)(3)(B)(i)........................................................................................ 3,5,8
21 USC 360(f) .......................................................................................................... 5
21 USC 360c(a)(2)(C) ......................................................................................... 5,14

Regulations
21 CFR 56.111(a)(2)(2006)...................................................................................... 8
Final Rule Declaring Dietary Supplements Containing Ephedrine Alkaloids
Adulterated Because They Present an Unreasonable Risk,
69 Fed.Reg. 6788 (Feb. 11, 2004).....................................................................passim

Other Sources
S.Rep. 103-410 (1994).................................................................................. 10,11,13
Statement of Agreement, 140 Cong. Rec. S14801 (Oct. 7, 1994),
reprinted in 1994 U.S.C.C.A.N. 352…………………………….......................…. 11

Nutraceutical Corporation and Solaray, Inc. (Nutraceutical) hereby petition for
rehearing or rehearing en banc of the panel decision filed Aug. 17, 2006. See Exhibit A.
STATEMENT OF COUNSEL UNDER F.R.A.P. 35(b)

The Decision conflicts with the Supreme Court's precedent governing statutory
construction.¹

____________________
¹ Those cases are Gonzales v. Oregon, 126 S.Ct. 904, 925 (2006); Whitaker v.
American Trucking Ass'n, 531 U.S. 457, 468 (2001); FDA v. Brown & Williamson
Tobacco, 529 U.S. 120, 133 (2000); Estate of Cowart v. Nicklos Drilling Co., 505 U.S.
469, 475 (1992); Demarest v. Manspeaker, 498 U.S. 184, 190 (1991); Chevron USA Inc.
v. Natural Resources Defense Council Inc., 467 U.S. 837, 842 (1984); and Russello v.
United States, 464 U.S. 16, 23 (1983).

In 1994, Congress amended the FDCA, 21 USC 321 et seq., with the DSHEA,
Pub.L.No. 103-417, 108 Stat. 4325 (1994). The DSHEA declares dietary supplements
(with one inapplicable exception) "foods" within the meaning of the FDCA. 21 USC
321(ff). In the Food Adulteration section, 21 USC 342, a dietary ingredient is adulterated
(and unmarketable) if it "presents a significant or unreasonable risk of illness or injury
under (i) conditions of use recommended or suggested in labeling . . ." 21 USC
342(f)(1)(A)(i). In a 2004 Rule FDA banned EDS at every dose level when present in
dietary supplements (but excepted ephedrine alkaloids regardless of dose when present in
foods) based on its reading of "unreasonable risk" in section 342(f)(1)(A)(i) of the Food
Adulteration section of the Act. 69 Fed.Reg. 6788, 6793 (Feb. 11, 2004). At trial and on
appeal, this case turned on construction of "unreasonable risk." Nutraceutical v.
Crawford, 364 F.Supp.2d 1310, 1318 (D.Ut. 2005) and Op. at 10. The District Court and
the panel each held "unreasonable risk" unambiguous, yet reached opposite conclusions
as to its "clear" meaning. Op. at 10-11; 364 F.Supp.2d at 1318. Nutraceutical is unaware
of any prior case in which two courts have applied Chevron Step 1 to the same statutory
language but have reached precisely opposite determinations of meaning.

The District Court held FDA's Rule a violation of section 342(f)(1)(A)(i),
explaining that the Rule depended on a risk-benefit comparison when nowhere in the
Food Title does Congress grant FDA authority to counterbalance risks with benefits;
rather, by its terms section 342(f)(1)(A)(i) only mentions risk. The District Court also
held, consistent with the statutory language ("conditions of use recommended or

suggested in labeling") that FDA had to evaluate the actual dietary ingredient, not a
hypothetical drug substitute, under actual conditions of use and determine the dose level
at which injury occurred (banning ephedrine alkaloids at that dose and above). The panel
reversed, upholding FDA's interpretation of "unreasonable risk," relying on Merck
KGaA v. Integra-Life Sciences I, Ltd., 125 S.Ct. 2372 (2005) (citing 21 USC
355(i)(3)(B)(i), the New Drugs' section of the Act), Op. at 11, and accepting as valid
FDA's reliance on a hypothetical drug model, not on the actual dietary ingredient at
actual dose levels. Op. at 17-19.

The panel decision effectively imposes the same risk-benefit comparison standard
in post-market review of dietary supplements that is reserved by statute for pre-market
review of drugs. The decision's impact extends far beyond a ban on EDS. It grants FDA
authority to declare any dietary ingredient adulterated on FDA's subjective assessment of
the adequacy of the ingredient's health benefits if FDA finds even so much as an
infinitesimal risk of illness or injury from ingestion of the ingredient (a ubiquitous
condition because all ingredients pose some risk at some dose).

The 1962 Kefauver-Harris Amendments to the FDCA decree that no drug may
lawfully enter the market unless FDA finds it safe and effective. Without any support
from text or legislative history, the panel invoked the surplusage canon (no term should
be treated as surplusage) to read the drug effectiveness requirement into the food
provisions of the Act governing dietary ingredients. Moreover, the panel condoned
FDA's application of that standard. At no point did FDA determine whether the
recommended concentrations at which EDS was sold (10 mg or less/day) posed the

unreasonable risk it purported to measure. Instead it evaded its burden of proof by
allowing extrapolations of risk to be made from the study of different substances (the
drugs epinephrine and ephedrine) in different concentrations and through different
methods of administration (continuous IV drip rather than oral ingestion). The Rule
forbids Nutraceutical from selling its low-dose EDS in a dietary supplement but allows it
to sell the very same substance (indeed, any amount of ephedrine alkaloids) in a tea bag.
The Rule thus renders the Food Adulteration section irrational and internally inconsistent:
what may not be sold as a dietary ingredient may be sold as a food.

In its Rule, FDA concluded that "unreasonable risk" meant "comparison of the
risks and benefits . . . ," 69 Fed.Reg. at 6823, "a relative weighing of the product's known
and reasonably likely risks against its known and reasonably likely benefits." Id. FDA
stated that "significant" and "unreasonable" had distinct meanings. "Significant"
involved risk alone, while "unreasonable" required a risk-benefit comparison, reasoning
that "[a] risk could be significant, but reasonable, if the benefits were great enough to
outweigh the risks." Id. The FDA deemed it unnecessary to determine if EDS presented
a "significant" risk, basing its decision exclusively on "unreasonable" risk. Id. at 6788;
6822-23. FDA declared "[i]n the absence of a sufficient benefit, the presence of even a
relatively small risk . . . may be unreasonable." Id. at 6788. FDA concluded that EDS
pose short and long-term risks and "[t]he data do not indicate that these products provide

a health benefit sufficient to outweigh these risks." Id. at 6789. There was no mention of
any other consumer benefits.² Therefore, FDA banned all EDS as "adulterated."
In its Rule and before the District Court, FDA relied on the FDCA's medical
device classification section, 21 USC 360c(a)(2)(C) (not the medical device banning
section, 21 USC 360(f), and not the New Drugs section, 21 USC 355(i)(3)(B)(i)), as
support for its argument that "unreasonable risk" meant a risk-benefit comparison. See
69 Fed.Reg. at 6823; 364 F.Supp.2d at 1318. That section, however, does not use the
term "unreasonable risk" and pertains to pre-market classification of medical devices. 21
USC 360c(a)(2)(C).

Before the panel, FDA shifted its reliance to the New Drugs section in 21 USC
355(i)(3)(B)(i), citing to Merck, 125 S.Ct. at 238. The panel agreed with FDA, also
citing Merck, Op. at 11, holding under Chevron Step 1 that "unreasonable risk" meant the
same as in the New Drugs section. The New Drugs section in Merck3 deals with patent
issues far removed from this dispute. Given these manifest differences, it is unsurprising
that neither the FDA Rule nor FDA in District Court relied on that New Drugs section to

² Assuming arguendo "unreasonable" means a risk-benefit comparison, FDA's approach
is still illogical. There is nothing in the term that requires FDA to ignore all other
benefits consumers attach to the consumption of a dietary supplement. The technical
measure of consumer welfare is equal to the price that consumers collectively would pay
over its cost in order to consume the product in question. Those subjective and psychic
components belong on the benefit side of any risk-benefit equation. But once those are
included, there is no basis for holding that a dietary supplement with an infinitesimal risk
does not produce a net benefit. That conclusion would not be proper for other foods, like
the potato chip example cited by the District Court, 364 F.Supp.2d at 1319 n.6, governed
under the identical statute.

³ In Merck, the Court examined 21 USC 355(i)(3)(B)(i), along with others, to determine
the scope of a safe harbor from patent infringement for preclinical testing necessary to
supply FDA information on a new drug. 125 S.Ct. at 2380-2381.

define "unreasonable risk." Rather, FDA first raised the argument before the panel. The
panel's reliance on that post hoc rationalization is forbidden. See, e.g., Citizens to
Preserve Overton Park, Inc. v. Volpe, 401 U.S. 402, 419 (1971).

The panel observed that "Congress enacted DSHEA to clarify that dietary
supplements . . . would be regulated . . . similar to food[s]," Op. at 11, and "to improve
public access to . . . supplements . . ." Id. (citation omitted). However, when the panel
addressed the meaning of "unreasonable risk," it disregarded those principles and
misinterpreted the statute. The panel engaged in a statutory tour-de-force, holding that
Chevron Step 1 required approval of the same statutory scheme that the District Court
struck down on summary judgment. In making this 180° switch, the panel held FDA had
manifest authority to evaluate the health benefits of dietary ingredients even for dietary
ingredients with an infinitesimal risk. The sole peg for the panel's rendition was its
aggressive reading of the words "unreasonable risk" within the following phrase in 21
USC 342(f)(1)(A)(i): "presents a significant or unreasonable risk of illness or injury
under - (i) conditions of use recommended or suggested in labeling." At trial and on
appeal, the case turned on the words "unreasonable risk." Nutraceutical, 364 F.Supp.2d
at 1318 and Op. at 10.

In the panel's view the single canon governing construction is that of
"surplusage." That formalist canon insists that each word within a provision carry a
meaning distinct from all others. The term "significant risk" clearly refers to risk
magnitude and ensures that miniscule risks associated with tiny levels of ingestion do not

constitute adulteration. The panel held the term "unreasonable risk" meant exclusively a
risk-benefit comparison as prescribed in the New Drugs section of the Act, Op. at 11;
however, by plain meaning in context the term does not beget that definition. In context,
a risk is unreasonable when a dietary ingredient reaches a dose level that causes illness or
injury.⁴ The surplusage canon may not be used to effect a meaning contrary to the one
plainly intended and here, without question, importation of the drug risk-benefit standard
into the food context violates Congress's plain intent.⁵ The panel reads "unreasonable
risk" out of context to require thorough investigation of dietary ingredient health benefits.
In so doing, it morphed the Food Adulteration section into the effectiveness review that
the FDCA requires only of drugs. That statutory tour-de-force reads out of section
342(f)(1)(A)(i) the requirement that adulteration be based on recommended or suggested
dosage (allowing adulteration to exist without a showing of harm at a particular dose and
recommended use).

Neither section 342(f)(1)(A) nor any DSHEA part mentions "potential benefits" in
determining whether a risk is unreasonable. The panel's only authority for its conclusion

⁴ By contrast, a "significant" risk is one that describes the degree of illness or injury
incurred (e.g., a tumor as opposed to a headache).
⁵ The surplusage canon cannot be used to interpret the law contrary to congressional
intent. Scheidler v. National Organization for Women, Inc., 126 S.Ct. 1264, 1273-1274
(2006); see also Lamie v. United States Trustee, 540 U.S. 526, (2004)(citing Chickasaw
Nation v. United States, 534 U.S. 84, 94 (2001)). Congress has made it crystal clear that
dietary supplements are to be regulated as foods, not drugs. 21 U.S.C. 321(ff); see
discussion 10-11 infra. Foods are not required to prove a benefit when faced with a claim
of adulteration. 21 U.S.C. 342. In FDA's pre-market evaluation, drugs are required to
prove a benefit to weigh against risk of harm. 21 U.S.C. 355(a).

is the drug case Merck. Op. at 11. Merck involved the meaning of "unreasonable risk"
in the "clinical hold" exception to the FDCA's New Drugs section. See 21 USC
355(i)(3)(B)(i). To be sure, the FDCA expressly requires FDA to undertake a riskbenefit
evaluation of new drugs, see 21 USC 355(b)(1)(A), so it is hardly surprising that
the FDA regulation on point, 21 CFR 56.111(a)(2)(2006), would incorporate a riskbenefit
test. By contrast, DSHEA includes no comparable express statutory provision for
a risk-benefit analysis of supplements. Merck is therefore inapposite.

The panel's interpretation of "unreasonable risk" utterly undermines the section's
systematic purpose by wrenching those two words out of context in ways that vastly
expand the FDA's power over dietary supplements. Food adulteration law is grounded in
the Paracelsian axiom that dose determines toxicity. All dietary ingredients pose a risk,
depending on dose. Thus, with that essential distinguishing principle and the plain
contextual meaning in mind, an "unreasonable risk" is defined as that dose level that
causes illness or injury and above. A "significant" risk is one that describes the degree of
illness or injury incurred (e.g., a tumor as opposed to a headache).

The panel accepted FDA's logic that even a slight risk justifies a finding of
adulteration if no substantial countervailing benefit exists. 69 Fed. Reg. at 6788. Thus
by giving "significant" no meaning, FDA may ban a dietary ingredient upon proof of
even the slightest risk at some dose level. It is axiomatic, however, that all substances
(even water) pose a risk at some dose level. See Fleming v. Florida Citrus Exchange, 358
U.S. 153, 163 (1958); see also United States v. Lexington Mill & Elevator Co., 232 U.S.
399, 411-412 (1914). Thus, the interpretation given removes from the law its dose

determines toxicity distinguishing principle, the principle that gives meaning to the
"conditions of use" requirement in 21 USC 342(f)(1)(A)(i) (that risk be assessed based on
the actual ingredient at doses recommended). On the panel's logic, there could be at
most an infinitesimal risk of some injury and still the dietary ingredient would be
unlawful if FDA opines that the health benefits of the ingredient are insubstantial. That
rationale affords no real protection to supplements. It flouts DSHEA statutory findings
that "dietary supplements are safe within a broad range of intake . . ." and that legislative
action is needed to protect "the right of . . .consumers to safe dietary supplements . . ."
Pub. L. 103-417, Sec. 2, Findings at paras. 14, 15(A). On the panel's logic, there is never
a reason for FDA to deal with "significance" of risk. Op. at 14. Risk significance is
immaterial (any risk will do). The dose determines toxicity concept has been written out
of the law; regardless of dose, a slight risk at some dose in the absence of a substantial
benefit is now grounds for finding adulteration.⁶

In addition, the aggressive reading of this provision undermines the requirement
that FDA bear the burden of proof to demonstrate that the dietary ingredient is
adulterated under the statute for its use at a specific concentration. 21 USC 342. That
individuated determination cannot be supported by extrapolating from studies not

⁶ Because the statute places the burden of proof on FDA, 21 USC 342(f)(1), the shift
from proof of risk significance to benefit significance causes the overall adulteration
determination to turn on the extent of benefit, not of risk. The risk side of the equation is
a given; the ultimate outcome is now to be decided based on FDA's subjective perception
of benefit.

involving any field or clinical findings concerning the specific dietary ingredient at the
dosages recommended.⁷

C. The Panel's "Unreasonable Risk" Definition Violates the Supreme Court's
Statutory Construction Precedent

FDCA's Food Adulteration section nowhere mentions a comparison of risks and
benefits. The panel nevertheless holds "unreasonable risk" "to connote" that comparison
not based on precedent governing dietary ingredients but based on precedent governing
new drugs. The panel thus reaches beyond anything in the Act that governs foods to the
New Drugs section for a definition that will govern when a dietary ingredient may be
removed from the market. That reach goes too far. It upsets the statutory distinction
between foods, including dietary ingredients (which are presumed safe and marketable
based on historic use in the food supply), and drugs (which are presumed unsafe and
unmarketable until proof of efficacy is shown to exceed proof of risk). See 21 USC 342,
350b, 321(p), 355.

The FDCA creates distinct food and drug regulatory regimes. Foods need only be
safe to be marketed (proof of benefit is not required). See 21 USC 342. Drugs must be
both safe and efficacious (proof of efficacy is required). 21 USC 321(p), 355. Dietary
ingredient adulteration arises in the Food Adulteration section (21 USC 342; 342(f)). The

⁷ Nutraceutical's argument is bolstered by the detailed committee report for this statute
which at every point reveals Congress's antipathy toward FDA's efforts to restrict the
availability of dietary supplements. At several points the report affirms the soundness of
decisions rebuking FDA for its aggressive positions, S.Rep. 103-410, at 21, 22 (1994),
agreeing with the description of the Circuit Courts deeming FDA's actions "nonsense"
and an "Alice-in-Wonderland" approach.

FDCA deems supplements "food[s] within the meaning of this Act." 21 USC 321(ff).
There is no FDCA language (and none in the legislative history, S. Rep. 103-410 (1994))
directing FDA to treat dietary ingredients like drugs for adulteration purposes. To the
contrary, Congress insists that dietary supplements be regulated as "foods:" "[Section
321(ff)] is intended to be explicit about a point that ought to be clear . . . : a product
intended . . . to supplement the diet with any . . . herb . . . is subject to regulation as a
food and not as a drug," S. Rep. 103-410 at 19; ". . . FDA has attempted . . . to assert that
. . . dietary ingredients are drugs based solely on their composition . . . [;] [t]his has led to
inconsistent . . . treatment of . . . supplements as drugs . . . ," Id. at 19; and "[t]he
committee intends that . . . FDA . . . regulate dietary supplements as food . . . not as drugs
. . ." Id. at 20.⁸ There is no FDCA language directing FDA to abandon its focus in food
adulteration on risk of the dietary ingredient under actual conditions of use.⁹

⁸ In a "Statement of Agreement" in the congressional record after the Senate Report but
before the vote on DSHEA, nine bill sponsors stated their "intent" that "no other reports
or statements be considered as legislative history for the bill." 140 Cong. Rec. S14801
(Oct. 7, 1994), reprinted in 1994 U.S.C.C.A.N. 352. The Statement is invalid as an attempt to
replace the Senate Report; the opinion of nine bill sponsors, after the Senate Report in
support of the bill was voted out of committee, cannot undo the legislative significance of
that majority committee report. See Garcia v. United States, 469 U.S. 70, 76, 76n.3
(1984) (authoritative source for legislative history is the committee reports, not floor
statements). In Pharmanex v. Shalala, 221 F.3d 1151, 1158 (10th Cir. 2000), this court
recognized the Statement of Agreement, expressly did not "pass[] on the legitimacy or
effectiveness of" it, 221 F.3d at 1158, and considered the Senate Report despite it. Id.

⁹ See, e.g., United States v. Anderson Seafoods, 622 F.2d 157, 162 (5th Cir. 1980) (FDA
failed to prove mercury adulteration in fish because agency relied not on actual
conditions but on general mercury science); United States v. Boston Farm Center, 590
F.2d 149 (5th Cir. 1974) (FDA failed to prove aflatoxin adulteration in corn because
agency relied not on actual conditions but on general aflatoxins science).

In construing statutory language, the Supreme Court expects agencies to give
effect to every word, not render words such as "significant" and "conditions of use
recommended or suggested in labeling" meaningless. See Estate of Cowart, 505 U.S. at
475 (citing Demarest, 498 U.S. at 190). The Court presumes Congress intends no
fundamental change in existing law unless Congress makes that intention clear in the
language of the Act itself. See Gonzales, 126 S.Ct. at 925; see also American Trucking
Ass'n, 531 U.S. at 468 ("Congress . . . does not alter the fundamental details of a
regulatory scheme in vague terms or ancillary provisions-it does not, one might say,
hide elephants in mouseholes"). Here the shift from risk (the historic food model) to a
comparison of risk and benefit (the historic drug mode of analysis) is, pure and simple, an
extra-statutory reach by FDA, a raw usurpation that treats the term "unreasonable" as the
proverbial elephant in the mousehole. The Supreme Court instructs that "where Congress
includes particular language in one section of a statute but omits it in another . . ., it is
generally presumed that Congress acts intentionally and purposely in the disparate
inclusion or exclusion." Russello, 464 U.S. at 23. Surely had Congress intended so
radical a move as the adoption of the New Drugs risk-benefit analysis for dietary
ingredient adulteration, it would have said so plainly in the Act,¹⁰ by using parallel
provisions to the effectiveness language that Kefauver-Harris introduced for drugs. The
Supreme Court expects statutes to be interpreted to be rational; the law abhors internal

¹⁰ The absence of language directing FDA to adopt risk-benefit is telling because
elsewhere when Congress intended that interpretation it supplied it expressly. Cf. 21
USC 342(f)(1)(A)(i) and 21 USC 360c. See also American Textile Mfr. Inst. v.
Donovan, 452 U.S. 490, 510 (1981)(When Congress intends a cost-benefit analysis, it
indicates that intent "on the face of the statute").

inconsistency. See Brown & Williamson Tobacco Corp, 529 U.S. at 133 (courts must
interpret the statute "'as a symmetrical and coherent regulatory scheme' and 'fit, if
possible, all parts into a harmonious whole'") (citations omitted). FDA's Rule produces
the absurd result of causing raw crushed ephedra sinica herb to be unlawful when placed
in a gelatin capsule but legal when placed in a tea bag. The Rule thus renders the Food
Adulteration provision internally inconsistent. Dietary ingredients in supplements are
held to a drug risk-benefit standard but the very same ingredients in foods are held
exclusively to a risk standard.

In DSHEA Section 2 (Findings), Congress explained that nearly
"50 percent of . . . Americans regularly consume dietary supplements" and that the
supplement industry is "an integral part of the [U.S.] economy . . ." Pub. L. 103-417, 108
Stat. 4325, 4326 ((9) and (12)(A)). Congress meant to protect public access to dietary
ingredients at safe dose levels. 108 Stat. at 4326 (15)(A); S.Rep. 103-410 at 36 ("a safety
finding cannot be entered against a supplement based upon a dosage not recommended in
the labeling"). The Rule upheld by the panel is the first to ban a dietary ingredient at
every dose level based on an assessment in which even a slight risk is sufficient to justify
that draconian action unless FDA finds a substantial countervailing benefit. With that
low risk threshold and subjective benefit balancing-a test liberated from the need to
prove the dose at which toxicity occurs-FDA may in its discretion remove virtually any

dietary ingredient from the market.¹¹ To quote FDA, "[i]n the absence of a sufficient
benefit, the presence of even a relatively small risk . . . may be unreasonable." 69
Fed.Reg. at 6788.¹² Small, for these purposes, means any risk greater than zero, which is
any risk at all.

The panel has given FDA unprecedented power to declare a dietary ingredient
adulterated even down to a molecule (i.e., even at unquestionably safe doses) when proof
of illness or injury only exists at many times that dose. The result is an extraordinary
power to constrict the availability of dietary ingredients even at safe doses, an end
opposite the DSHEA aim of protecting consumer access to supplements at those doses.

Moreover, the argument that "unreasonable risk" "obviously" connotes
exclusively a risk-benefit comparison is belied by FDA's shifting reliance. In the Rule

¹¹ The Rule banned all EDS, even down to a molecule. The ban is not based on testing of
the actual dietary ingredient at Nutraceutical's dose (10mg or less/day) as required by the
statute ("under conditions of use recommended . . . in labeling," 21 USC 342(f)(1)(A)(i))
but on a hypothetical drug comparison model, an untested, unpeer-reviewed extrapolation
from unrelated tests of the drugs epinephrine and ephedrine to the dietary ingredient
ephedrine alkaloids. In unpeer-reviewed letters, one Dr. Mario Inchiosa speculated from
intravenous drug studies that the pharmacologically different non-drug substance,
ephedrine alkaloids, when orally ingested at 1.5 mg every four hours continuously would
raise heart rate and blood pressure akin to the drugs. Appellants' App. at 218. The proof
did not test the dietary ingredient at all, let alone at specific doses recommended in
labeling. Reliance on hypothetical drug comparison models does not satisfy FDA's
"burden of proof on each element" including "conditions of use recommended . . . in
labeling" required by the statute.

¹² The Paracelsian dose determines toxicity axiom, articulated in the Supreme Court's
earliest food adulteration decision, Lexington Mill & Elevator Co., 232 U.S. at 411-412,
and reiterated in food decisions ever since (see, e.g., Anderson Seafoods, 622 F.2d 159) is
the irreducible distinguishing principle in determining whether a food or dietary
ingredient based on conditions of use is adulterated. Risk is immaterial until we reach
that dose at which illness or injury occurs. The division between a lawful and an
adulterated dietary ingredient is that very dose level and above.

and before the District Court, FDA argued "unreasonable risk" meant the same as
Congress provided in the medical device classification section, 21 USC 360c (where, in
fact, the term "unreasonable risk" does not appear), and meant the same as Congress
specified in the Toxic Substances Control Act despite the obvious inapplicability of that
law to the FDCA. On appeal, however, FDA shifted its reliance with a post hoc
rationalization: identifying the New Drugs section's clinical hold exception (cited in
Merck, 125 S.Ct. 2372) as defining "unreasonable risk." The panel agreed with FDA and
relied on that same drug section, thus causing arguments first raised on appeal to be
accepted as the decisional rationale, post hoc, when the Rule contains no such basis. The
courts of appeal, including this court, prohibit post hoc rationalizations of this kind;¹³ the
panel decision is predicated centrally on this forbidden rationale.

For the foregoing reasons, Nutraceutical Corporation respectfully requests that this
Honorable Court grant rehearing or rehearing en banc of the panel decision.

Respectfully submitted,
NUTRACEUTICAL CORPORATION AND
SOLARAY, INC.

By:________/s/________________
Jonathan W. Emord*
Andrea G. Ferrenz
Emord & Associates, P.C.
1800 Alexander Bell Drive, Suite 200
Reston, VA 20191

¹³ The record on appeal of an administrative agency rulemaking is "frozen." Neither the
FDA nor parties appealing the rule may introduce for the first time post hoc
rationalizations for the rule. See Citizens to Preserve Overton Park, 401 U.S. at 419
(citations omitted).

Marcy G. Glenn
Susan L. Lyndrup
Holland & Hart
555 Seventeenth Street, Suite 3200
Denver, CO 80202-3979